Over the past few years, due to the significant expansion of the biopharmaceutical field, stricter validation standards, and a better comprehension of Quality by Design (QbD) and Process Analytical Technology (PAT), the need for aseptic sampling has grown. Conventional sampling techniques, such as glass vials and Steam In-Place Sterilization (SIP) stainless steel valve sampling, have become inadequate, and closed sampling approaches have evolved and are now commonly employed.

Regulatory agencies mandate that drug sampling methods comply with relevant regulations, in addition to ensuring contamination control and drug safety. Here are some common application scenarios for closed aseptic sampling systems:

	Buffer Media Configuration	Bioreactor Seed Tank	Bioreactor Production Tank	Sterile Filtration	Purification/ Semi-Manufactured Goods	Filling
pH	√	√	√	√	√	√
Conductivity	√	√	√	√	√	√
Osmolality	√	√	√	√	√	√
Cells (Number, Viability)		√	√
Metabolite		√	√
Protein Analysis			√	√	√	√
Endotoxin	√	√	√	√	√	√
Concentration				√	√	√
Other	√	√	√	√	√	√

Requirements of The Statute

Compared to the cost of pharmaceutical contamination, the expense of sterile sampling is low. Regulatory agencies such as FDA, WHO, and EU GMP, as well as industry associations like PDA and PIC/S, offer guidance and recommendations to assist biopharmaceutical companies in transitioning from traditional sampling to aseptic sampling solutions.

211.84 Testing and approval or rejection of components, drug product containers, and closures.

(C) Samples shall be collected in accordance with the following procedures:

1. The containers of components selected shall be cleaned where necessary, by appropriate means.
2. The containers shall be opened, sampled, and resealed in a manner designed to prevent contamination of their contents and contamination of other components, drug product containers, or closures.
3. Sterile equipment and aseptic sampling techniques shall be used when necessary.
4. If it is necessary to sample a component from the top, middle, and bottom of its container, such sample subdivisions shall not be composited for testing.
5. Sample containers shall be identified so that the following information can be determined: the name of the material sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and the name of the person who collected the sample.
6. Containers from which samples have been taken shall be marked to show that samples have been removed from them.

Common Aseptic Sampling Methods

Needlefree Swabable Valve

Features:

• When installing, connect the female valve to a matching locking male luer lock fitting. This will automatically stop the flow of fluid, preventing any drips or leaks when disconnected. No clip is needed with this design;
• Low pre-charge capacity & high flow;
• Straight-through design ensures smooth flow,
• Transparent material for easy viewing of the fluid path;
• Repeatable sampling.

Applications: 

Process sampling of bioreactor seed tanks, aseptic dosing, aseptic post-filtration solution, etc.

Sampling Plug

Features:

• Using a sampling needle to puncture and stop the liquid with automatic sealing;
• Sampling by needle syringe;
• Repeatable sampling.
• Applications: 
• Blood products, medical supplies, cell therapy sampling.

Sampling Plug, ф20mm

Features:

• Providing access and injection port primarily for infusion;
• Conducting simultaneous multi-channel sampling using equipment;
• Repeatable sampling.
• Applications:
• Bacteria collectors, medical supplies, etc.

Luer Lock

Features:

• Sampling by connecting male and female luer connectors;
• Suitable for connecting all types of small-diameter tubing and works with gas-liquid medium universally;
• Can be used with luer syringes;
• Screwing design, convenient and risk-free;
• Repeatable sampling.

Applications:

Purification, laboratory equipment, biochemical testing, medical supplies and other rapid, non-sterile sampling operations.

Sampling Needle

Features:

• Using by matching sampling base, SIP；
• Stainless steel system allows in-line sterile sampling；
• Multiple preset sampling paths can be selected with the sampling bag；
• The integrity of the entire tank or closed tubing is not compromised before or after sampling;
• No dead spots or residues at sampling points.

Applications:

Bioreactor, seed tank, fermenters, formulation tanks, etc.

Conclusion

Cobetter provides safe and versatile sampling solutions that offer several advantages over traditional sampling programs.

• Our self-produced joints, supports, and sampling containers come in various configurations that can be flexibly matched to meet the needs of different production processes in various fields.
• We have a professional design team and injection molding team that work together to improve the rationality of the design and application. We also provide complete material screening and functional testing services.
• Our perfect verification capability allows us to provide functional test documents, E&L documents, chemical compatibility documents, and extreme application documents, which reduces your worries and risks.

Compliant aseptic sampling should be able to obtain the most representative samples in a closed environment while ensuring the safety of the environment, product and operator, and can be combined with stainless steel tanks, single-use tubing and assemblies. Cobetter offers compliant, rational, convenient and feasible sampling solutions throughout the entire biopharmaceutical manufacturing process, from culture media preparation, seed culture, and sterile filtration to filling.